Initial Treatment

Surgery for Operable Disease | Neoadjuvant Gleevec | Adjuvant Treatment | Unrectable or Metastatic Disease | Where Should Patients be Treated? | References

Most GIST patients will only have a single tumor at the time of diagnosis. A significant minority however, will already have metastases at the time of diagnosis. Initial treatment will be dependent on several factors including:

• Whether a patient has metastases or not
• The expected difficulty of the surgery
• The size of the primary tumor
• The general health of the patient

Surgery for Operable Disease

Surgery is typically the standard initial treatment for GIST. In some cases, a patient might have had surgery to remove a mass and received a GIST diagnosis after surgery. In other cases, Gleevec may be given prior to surgery with the goal of reducing the size of the tumor(s) to make surgery easier. This is called "neoadjuvant Gleevec".

According to the recent Journal of National Comprehensive Cancer Network guidelines on GIST , (primary) GISTs greater than 2cm in size should be removed (resected), however, the management of incidentally encountered GISTs less than 2 cm in size remains controversial¹. Long-term follow-up of a large number of GIST patients found little or no risk of progressive disease (metastasis or tumor-related death) with primary tumors less than 2 cm in size.

Surgery for primary GIST offers the best chance of a "cure" or long-term benefit. The risk of a recurrence after surgery is related to the tumor size, how fast the tumor is growing (mitotic rate) and tumor location. See the diagnosis section for details.

GIST tumors are often surrounded by a "pseudocapsule". The goal of surgery is complete removal of the tumor with an intact pseudocapsule. The margins of the resected tissue should be free of tumor (negative microscopic margins).

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Neoadjuvant Gleevec

Some patients that don't have metastatic disease will have large or difficult to remove tumors at the time of diagnosis. In cases where surgery seems likely to cause significant loss of function (such as the total removal of the stomach) medical treatment with Gleevec can be considered prior to surgery. Gleevec has a high response rate with about 2/3 of patients experiencing significant shrinkage (see the table below). Patients must be monitored closely to insure that they are not progressing. According to the JNCCN guidelines; " Patients can be treated with imatinib until the optimal time for surgery (when the GIST becomes resectable and the chance of morbidity is acceptable), which can take as long as 6 to 12 months." According the the JNCCN guidelines, "For both large tumors and poorly positioned small GISTs that are considered marginally resectable on technical grounds, neoadjuvant imatinib is recommended. Patients with primary localized GIST whose tumors are deemed unresectable should also
start imatinib."

Note: A phase II neoadjuvant trial (RTOG-S0132) is closed to recruitment. This trial is ongoing but not recruiting patients. The early results were published in the Journal of Surgical Oncology.

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Adjuvant Treatment

Many GIST patients have surgery to remove a primary tumor and do not have detectable metastases at the time of surgery. On December 19th, 2008, the FDA approved Gleevec as adjuvant therapy for patients in the United States. Adjuvant therapy refers to additional treatment given after a main mode of therapy (the main treatment is usually surgery). For example, Gleevec given after surgery in hopes of preventing or delaying a recurrence is called adjuvant therapy. For further discussion about adjuvant treatment with Gleevec see the Preventative Treatment section of this website.

Unresectable or Metastatic Disease

Gleevec is the standard treatment for unresectable or metastatic GIST. If an unresectable primary tumor undergoes significant shrinkage after treatment with Gleevec, then surgery can be reconsidered. With metastatic GIST, Gleevec is continued lifelong or until progression. Patients that can't tolerate Gleevec can try Sutent (approved for Gleevec-resistant GIST or GIST patients that can't tolerate Gleevec in many countries).

Where should patients be treated?

The following recommendation comes from the JNCCN guidelines:

"In general, patients should be managed by a multidisciplinary team with expertise in sarcoma or tumors of the GI tract. However, referral of patients with early stage or straightforward, uncomplicated metastatic disease to such specialists may not always be essential. However, all cases should be presented at a tumor board whenever possible. Any GIST patient with complicated or unusual features or those patients with advanced refractory disease should be appropriately referred to a center with specialty expertise and experience in the management of GIST ¹.

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References

1.NCCN Task Force Report: Optimal Management of Patients with Gastrointestinal Stromal Tumor (GIST)—Update of the NCCN Clinical Practice Guidelines (July, 2007)

George D. Demetri, MD; Robert S. Benjamin, MD; Charles D. Blanke, MD; Jean-Yves Blay, MD, PhD; Paolo Casali, MD; Haesun Choi, MD; Christopher L. Corless, MD, PhD; Maria Debiec-Rychter, MD, PhD; Ronald P. DeMatteo, MD; David S. Ettinger, MD; George A. Fisher, MD, PhD; Christopher D.M. Fletcher, MD, FRCPath; Alessandro Gronchi, MD; Peter Hohenberger, MD, PhD; Miranda Hughes, PhD; Heikki Joensuu, MD; Ian Judson, MD, FRCP; Axel Le Cesne, MD; Robert G. Maki, MD, PhD; Michael Morse, MD; Alberto S. Pappo, MD; Peter W.T. Pisters, MD; Chandrajit P. Raut, MD, MSc; Peter Reichardt, MD, PhD; Douglas S. Tyler, MD; Annick D. Van den Abbeele, MD; Margaret von Mehren, MD; Jeffrey D. Wayne, MD; and John Zalcberg, MBBS, PhD

2. Outcome of Advanced Gastrointestinal Stromal Tumor (GIST) Patients Treated With Imatinib Mesylate:Four-Year Follow-Up of a Phase II Randomized Trial Poster PDF 71KB ASCO 2006 Presentation